A Highly Complex Chromosomal Rearrangement between Five Chromosomes in a Healthy Female Diagnosed in Preparation for Intracytoplasmatic Sperm Injection

Kuechler, Alma; Ziegler, Monika; Blank, Cornelia; Rommel, Birgit; Bullerdiek, J.; Ahrens, Jochen; Claussen, Uwe; Liehr, Thomas

doi:10.1369/jhc.4b6437.2005

Cited by 20 publications

(15 citation statements)

References 11 publications

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“…Since DSB-containing chromosome domains have only limited mobility, chromosome domains in each other's vicinity would be more often involved, and chromosome domains located far apart in the gamete interphase nucleus are less likely to be involved in the same CCR. So in general more breakpoints than chromosomes should be involved in CCRs, an expectation that seems to be confi rmed by this report and other recent high-resolution analysed CCRs (Houge et al, 2003;Weise et al, 2003;de Vries et al, 2005;Gribble et al, 2005;Kuechler et al, 2005;Rosenberg et al, 2005). A single 'catastrophic' event causing multiple chromatin breaks could thus explain the origin of CCRs and other non-recurrent chromosomal aberrations (NRCAs).…”

Section: Discussionsupporting

confidence: 78%

Molecular cytogenetic characterization of a constitutional complex intrachromosomal 4q rearrangement in a patient with multiple congenital anomalies

Thienpont

Gewillig

Devriendt

et al. 2006

Cytogenet Genome Res

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Constitutional Complex Chromosomal Rearrangements (CCRs) are very rare. While the vast majority of CCRs involve more than one chromosome, only seven cases describe CCRs with four or more breakpoints within a single chromosome. Here, we present a patient with multiple congenital anomalies and mental retardation. Array Comparative Genomic Hybridisation (array CGH), FISH and Multicolour Banding FISH revealed a de novo complex rearrangement with two deletions, a duplication and an inversion of 4q. This CCR involving at least seven breakpoints is one of the most complex rearrangements of a single chromosome reported thus far. Potential mechanisms generating such complex rearrangements are discussed.

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Section: Discussionsupporting

confidence: 78%

Molecular cytogenetic characterization of a constitutional complex intrachromosomal 4q rearrangement in a patient with multiple congenital anomalies

Thienpont

Gewillig

Devriendt

et al. 2006

Cytogenet Genome Res

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“…However, similar to the aforementioned and discussed discordance of GTG-banding and molecular cytogenetic results confronted within this study there are few comparable cases available in the literature. What can be deduced from the literature is, that complex chromosomal rearrangements as in cases 10 and 30 are relatively rare events in infertility cases and can involve up to 5 or more different chromosomes (16)(17). The most complex rearrangement observed in this study was case 30 involving chromosome X, Y and 11.…”

Section: Types Of Rearrangements Observedmentioning

confidence: 47%

Forty-eight new cases with infertility due to balanced chromosomal rearrangements: Detailed molecular cytogenetic analysis of the 90 involved breakpoints

Manvelyan¹,

Schreyer²,

I³

et al. 2007

Int J Mol Med

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Abstract. A molecular cytogenetic study was performed on 48 infertile patients who were identified as carriers of balanced translocations (40 cases), inversions (6 cases) or insertions (2 cases) by means of banding cytogenetics. Cases with a Robertsonian translocation or pericentric inversion 2 or 9 were not included. In summary, 100 break-events occurred in these patients, and 90 different chromosomal regions were involved. Thus, this study confirmed the presence of abnormal karyotypes in a subgroup of patients seeking infertility treatment. Breaks were demonstrated to appear preferentially in GTG-light bands in these patients. Furthermore, the observed breakpoints were associated with genomic regions prone to instability due to the presence of segmental duplications. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.

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“…These authors divided CCRs in 2 broad groups: one group ≤ 4 breaks and the other group >4 breaks. They observed that most familial CCRs belonged to the group with up to 4 breaks and have been transmitted by a balanced female carrier, whereas most of the de novo CCRs belonged to the group with more than 4 breaks and were of paternal origin [Kousseff et al, 1993;Batista et al, 1994;Joyce et al, 1999;Lee et al, 2002;Grasshoff et al, 2003;Kuechler et al, 2005]. The majority of the reported cases had 4 or less breaks [Pellestor et al, 2011].…”

Section: Definition and Classification Of Ccrsmentioning

confidence: 99%

Mechanisms of Origin, Phenotypic Effects and Diagnostic Implications of Complex Chromosome Rearrangements

Poot

Haaf

2015

Mol Syndromol

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Complex chromosome rearrangements (CCRs) are currently defined as structural genome variations that involve more than 2 chromosome breaks and result in exchanges of chromosomal segments. They are thought to be extremely rare, but their detection rate is rising because of improvements in molecular cytogenetic technology. Their population frequency is also underestimated, since many CCRs may not elicit a phenotypic effect. CCRs may be the result of fork stalling and template switching, microhomology-mediated break-induced repair, breakage-fusion-bridge cycles, or chromothripsis. Patients with chromosomal instability syndromes show elevated rates of CCRs due to impaired DNA double-strand break responses during meiosis. Therefore, the putative functions of the proteins encoded by ATM, BLM, WRN, ATR, MRE11, NBS1, and RAD51 in preventing CCRs are discussed. CCRs may exert a pathogenic effect by either (1) gene dosage-dependent mechanisms, e.g. haploinsufficiency, (2) mechanisms based on disruption of the genomic architecture, such that genes, parts of genes or regulatory elements are truncated, fused or relocated and thus their interactions disturbed - these mechanisms will predominantly affect gene expression - or (3) mixed mutation mechanisms in which a CCR on one chromosome is combined with a different type of mutation on the other chromosome. Such inferred mechanisms of pathogenicity need corroboration by mRNA sequencing. Also, future studies with in vitro models, such as inducible pluripotent stem cells from patients with CCRs, and transgenic model organisms should substantiate current inferences regarding putative pathogenic effects of CCRs. The ramifications of the growing body of information on CCRs for clinical and experimental genetics and future treatment modalities are briefly illustrated with 2 cases, one of which suggests KDM4C(JMJD2C) as a novel candidate gene for mental retardation.

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A Highly Complex Chromosomal Rearrangement between Five Chromosomes in a Healthy Female Diagnosed in Preparation for Intracytoplasmatic Sperm Injection

Cited by 20 publications

References 11 publications

Molecular cytogenetic characterization of a constitutional complex intrachromosomal 4q rearrangement in a patient with multiple congenital anomalies

Molecular cytogenetic characterization of a constitutional complex intrachromosomal 4q rearrangement in a patient with multiple congenital anomalies

Forty-eight new cases with infertility due to balanced chromosomal rearrangements: Detailed molecular cytogenetic analysis of the 90 involved breakpoints

Mechanisms of Origin, Phenotypic Effects and Diagnostic Implications of Complex Chromosome Rearrangements

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